1. Field of the Invention
The present invention relates to a process for preparing pharmaceutically useful optically active 2-(6-methoxy-2-naphthyl)propionic acid, esters and pharmaceutically acceptable salts thereof. More specifically, it is concerned with a method of producing optically active intermediates which are useful in preparing the optically active 2-(6-methoxy-2-naphthyl)propionic acid, esters and pharmaceutically acceptable salts (preferably the sodium salt) referred to above.
2. State of the Art
The conventional procedures for preparing 2-(6-methoxy-2-naphthyl)propionic acid or esters thereof include the following methods:
(1) A method comprising subjecting 2-acetyl-6-methoxynaphthalene obtained by the Friedel-Crafts reaction of 2-methoxynaphthalene with acetyl chloride to the so-called Willgerodt-Kindler reaction using sulfur and morpholine to obtain (6-methoxy-2-naphthyl)acetic acid, converting the resulting compound into a methyl ester thereof, methylating the methyl ester using sodium hydride and methyl iodide to obtain methyl 2-(6-methoxy-2-naphthyl)propionate, and hydrolyzing the resulting compound with an alkali to obtain 2-(6-methoxy-2-naphthyl)propionic acid [refer to I. T. Harrison, B. Lewis, P. Nelson, W. Rooks, A. Roszkowski, A. Tomolonis, and J. H. Fried, J. Med. Chem., 13, 203 (1970)].
(2) A method comprising oxidizing 1-(6-methoxy-2-naphthyl)propene with thallium (Tl) oxide to produce 2-(6-methoxy-2-naphthyl)propanal which is then further oxidized with chromic acid to produce 2-(6-methoxy-2-naphthyl)propionic acid [refer to Japanese Patent Publication (Unexamined) No. 48648/74].
(3) A method comprising subjecting a Grignard reagent prepared from 2-bromo-6-methoxynaphthalene and magnesium metal, and a complex prepared from .alpha.-bromopropionic acid and methyl magnesium bromide to a so-called coupling reaction to produce 2-(6-methoxy-2-naphthyl)propionic acid [refer to Japanese Patent Publication (Unexamined) No. 111018/78].
(4) A method comprising reacting a solution of formaldehyde dimethylmercaptal S-oxide in tetrahydrofuran with successively butyl lithium, 2-acetyl-6-methoxynaphthalene and acetic anhydride at a low temperature, i.e., -78.degree. C. to -20.degree. C., to produce 1-methylsulfinyl-1-methylthio-2-acetoxy-2-(6-methoxy-2-naphthyl)propane, treating the resulting compound with sodium methoxide to obtain 1-methylsulfinyl-1-methylthio-2-(6-methoxy-2-naphthyl)-1-propene, and subjecting the propene compound to methanolysis using a hydrogen chloride catalyst to produce methyl 2-(6-methoxy-2-naphthyl)propionate [refer to Japanese Patent Publication (Unexamined) No. 59647/78].
(5) A method comprising preparing a 2-(6-methoxy-2-naphthyl)propionic acid ester from a 1-(substituted-naphthyl)-2-bromo-1-alkanone [refer to G. Tsuchihashi, K. Kitajima, S. Mitamura, Tetrahedron Letters, 22, 4305 (1981)].
In order to produce naproxen, 2-(6-methoxy-2-naphthyl)propionic acid or an ester thereof obtained by the above methods must be finally subjected to optical resolution. [Refer, for example, to Japanese Patent Publication No. 14097/81.] However, such optical resolution is not advantageous from the economical standpoint since one-half of the dl pairs, i.e., (R)-2-(6-methoxy-2-naphthyl)propionic acid, is unnecessary and also complicated racemization steps are required to reuse the (R)-form. In addition, a very expensive reagent such as cinchonidine must be used for optical resolution. As a result of extensive studies to overcome such disadvantages accompanied with the optical resolution, the present inventors found the compounds of this invention represented by the formula (XI) above which can be converted into naproxen without using optical resolution.